18β-Glycyrrhetinic Acid Inhibits Methicillin-Resistant Staphylococcus aureus Survival and Attenuates Virulence Gene Expression

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) has become a major source of infection in hospitals and in the community. Increasing antibiotic resistance in S. aureus strains has created a need for alternative therapies to treat disease. A component of the licorice root Glycyrrhiza spp., 18␤-glycyrrhetinic acid (GRA), has been shown to have antiviral, antitumor, and antibacterial activity. This investigation explores the in vitro and in vivo effects of GRA on MRSA pulsed-field gel electrophoresis (PFGE) type USA300. GRA exhibited bactericidal activity at concentrations exceeding 0.223 M. Upon exposure of S. aureus to sublytic concentrations of GRA, we observed a reduction in expression of key virulence genes, including saeR and hla. In murine models of skin and soft tissue infection, topical GRA treatment significantly reduced skin lesion size and decreased the expression of saeR and hla genes. Our investigation demonstrates that at high concentrations GRA is bactericidal to MRSA and at sublethal doses it reduces virulence gene expression in S. aureus both in vitro and in vivo.

Pentacyclic triterpene derivatives possessing polyhydroxyl ring A inhibit Gram-positive bacteria growth by regulating metabolism and virulence genes expression

“…The virulence genes in this study contribute to hemolytic activity of B. subtilis and S. aureus to human, as well as potato scab disease caused by S. scabies [3,48].…”

Strategies for Circumventing Bacterial Resistance Mechanisms

“…As we transition from populations at particular risk of bacterial infection -such as the transplant recipient (Bodro et al 2013), the immunocompromised (Bow 2013), and the critically ill (Cohen 2013) -to the entire populations at risk, such may result from the entry of pathogenic bacteria into the food supply (Le Hello et al 2013), neither new structures nor new technologies may alone suffice to provide the antibacterial future. We will need to aggressively evaluate empirical opportunities, such as pursuing repurposed compounds that act to sensitize (Thorsing et al 2013) or to attenuate quorum sensing (Imperi et al 2013b;O'Loughlin et al 2013), virulence (Imperi et al 2013a;Long et al 2013), and efflux (Jiang et al 2013). Reassessing old discovery strategies as well as implementing new strategies will be required (Shapiro 2013;Tegos and Hamblin 2013).…”

Glycyrrhetinic acid and its derivatives in infectious diseases

“…In such studies, it was put forward that the bactericidal activity of GE against MRSA may be related to the inhibition of expression of selected virulence genes, among these, saeR and hla [28]. In a further study, evaluation was performed of the glycyrrhetinic acid activity against 55 hospital strains of S. aureus and 32 hospital strains of Actinobacillus actinomycetemcomitans isolated from patient specimens by culture methods.…”

“…Therefore, the use of plant extracts and phytochemicals possessing known antimicrobial properties can be of significance in therapy [30]. In work of this nature, glycyrrhetinic acid was recognized as a compound possessing antimicrobial properties [24,28,32,35].…”